Effect and molecular mechanism of mitochondrial solute carrier protein SLC25A26 inducing hepatoma cell senescence / 中国药理学通报

ABSTRACT

Aim To explore the regulatory effect of mitochondrial solute carrier protein SLC25A26 on senescence of hepatoma cells induced by methionine cycle metabolism. Methods HepG2 cell line was cultured in vitro. After hepatoma cell senescence was induced by toposide (2 [xmol • Ľ'), a positive drug for inducing cell senescence, methionine circulating metabolite SAM (0. 1 mmol • L " ') was treated. Western blot and Real-time PGR were used to detect the senescence indexes including pl6, p21, and HMGAl, and flow cytometry was used to detect cell cycle. Transfecting SLC25A26 overexpression plasmid, the effect of overexpressing SLC25A26 on the senescence indexes of hepatoma cells was detected by Western blot and immunofluorescence detection, and the level of SAM after overexpressing SLC25A26 was detected by the kit. The effect of overexpressing SLG25A26 on the senescence of hepatoma cells after SAM treatment was detected by Real-time PGR. Results Western blot and Real-time PGR showed that methionine cycle metabolism could weaken the senescence level of HepG2 cells induced by Etoposide, and flow cytometry showed that cell cycle was arrested in Gl phase; overexpression of SLG25A26 decreased the levels of SAM and SAH in cytoplasm of HepG2 cells, and exogenous SAM partially offset the aging effect of HepG2 cells induced by SLG25A26. Conclusions Promoting methionine cycle metabolism can inhibit hepatoma cells senescence; overexpression of SLG25A26 can induce hepatoma cells senescence; SLG25A26 can induce hepatoma cells senescence by regulating methionine cycle metabolism.